"Tipai-Ipai" is the common name since the 1950s of two linguistically related groups formerly known as Kamia (Kumeyaay) and Diegueño. Both terms mean "People." "Diegueño" comes from the Spanish mission San Diego de Alcala. "Kamia" may have meant "those from the cliffs." The Tipai-Ipais are sometimes referred to as Diegueño Mission Indians.

During the late eighteenth century, the TipaiIpai lived in southern California and Baja California, along the coast and inland almost to the Colorado River. Today, many live on thirteen reservations in San Diego County, California. The late eighteenth-century Tipai-Ipai population stood between 3,000 and 9,000. Diegueño is a member of the Yuman division of the Hokan language family.

People have been living in traditional Tipai-Ipai territory for roughly 20,000 years. A proto–Tipai-Ipai culture had been established by about 5000 BCE, and the historic Tipai-Ipais were in place about 1,000 years ago.

Shamans were the religious leaders. They performed ceremonies, interpreted dreams, were believed to control weather, and cured the sick. Evil shamans might also produce disease. Named song cycles were associated with certain ceremonial dances. Ground paintings, a feature illustrating the connection with Southwestern cultures, featured symbols of colors and their associated directions. Their most important religious ceremony was kaurk. This clan-based mourning ceremony lasted from four to eight days. It included gift giving, dancing with images of the dead, and feasting, and it culminated with the burning of effigies of the dead. Toloache, a hallucinogenic root, was used by adolescent boys and adult men for spiritual strengthening.

The Tipai-Ipais consisted of over thirty autonomous bands or tribelets, usually made up of a single patrilineal clan and headed by a clan chief and an assistant. Neither the tribe nor the band had a formal name. Positions of authority were sometimes inherited by the eldest sons, brothers, and, rarely, widows. Two tribal chiefs directed ceremonies, advised about proper behavior, and appointed war or gathering leaders. Band leaders and councils saw to resource management. In historic times, some chiefs ordered assistants to beat nonconformists. The Imperial Valley Tipais had a tribal chief but no clan chief.

The Tipai-Ipais' food staple was flour made from six varieties of acorn as well as from mesquite beans and seeds of sage, pigweed, peppergrass, flax, and buckwheat. Flour was cooked into mush and cakes and stewed with meat and vegetables. Other wild foods included cactus, agave, clover, cherries, plums, elderberries, watercress, manzanita berries, piñon nuts, and prickly pear. People fished where fish were available. Animal foods, which were generally roasted on coals or in ashes, included rodents and an occasional deer. The people also ate lizards, some snakes, insects, larvae, and birds. They also cultivated tobacco, which only men smoked. Imperial Valley Ipais planted maize, beans, and teparies, but they placed greater emphasis on gathering.

In 1769, the Spanish built the presidio and mission of San Diego de Alcala and began rounding up local Indians, especially those to the north and on the coast. The latter revolted regularly. In 1775, about 800 people from some seventy villages united to burn the mission. It was later rebuilt, however, and the missionization process continued. After the Mexicans secularized the missions in 1834, they treated the resident Tipai-Ipais as trespassers or rebels and continued many of the same oppressive practices that characterized mission life.

In 1852, shortly after the United States gained control of California, the U.S. Senate ratified a treaty with "the nation of Diegueño Indians," under which the latter lost their best lands. Overgrazing and water diversions soon destroyed their remaining grassland and woodland. By the late 1870s, the Tipai-Ipais were settled on about twelve small, poor reservations, although many were at least located on the site of Native villages. Coastal Ipais also lived in San Diego slums or camped in nearby hills.

At the turn of the century many Tipai-Ipais were working for low wages on ranches and in mines and towns or starving on the inadequate reservations. Traditional Tipai-Ipai government was disrupted by Indian agents who required the Indians to select a "captain." Bitter political factions had emerged by the 1930s with the formation of the rival Mission Indian Federation and the Southern Mission Indians. Frequent cross-border visits and ceremonies became difficult after 1950 and impossible after the 1970s, owing to U.S. immigration policies. In recent times, the bands have been reviving the traditional governing structure.